This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project III: Fox The aim of this research program is to develop stereo- and enantioselective methods for using cyclopropenes and bicyclobutanes to prepare small ring analogs amino acids. Cyclopropyl and cyclobutyl amino acids have important biomedical applications and should find application in protein design. However, the existing synthetic methods give access to a limited range of functional groups and substitution patterns. The new approach is of significance to national interests in the health related sciences because the current state of the art does not permit small ring amino acids to be prepared easily or in variety. Accordingly, the specific aims of this proposal are to develop the following: (1) general methods for the Cu-catalyzed carbometallation reactions of cyclopropenes that proceed with either syn or anti selectivity. (2) procedures that convert the cyclopropyl anions from Aim 1 to cyclopropyl amines. (3) methodology that permits the incorporation of biologically relevant functional groups into these scaffolds. (4) an enantioselective deprotonation route for the asymmetric synthesis of cyclopropenes. (5) an enantioselective version of (1) and application to the synthesis and cyclopropyl amino acids. (6) protocols that convert enantiomerically enriched cyclopropenes to bicyclobutanes, and subsequently to cyclobutane amino acid derivatives.